3New Opportunities at the Nanoscale and at the Interface Between Biology and the Physical and Engineering Sciences

In addition to developing a broad mission statement and guidelines for selecting topics in new research areas (see Chapter 2), the Committee on Microgravity Research was also asked in this Phase I task to identify in general terms the research opportunities in the newly added discipline areas that could appropriately be pursued by the program.1 These new areas encompass still-emerging fields and thus can be characterized in various ways. In this report, they are referred to as nanoscale materials and processes, biomolecular physics and chemistry, cellular biophysics and chemistry, and integrated systems for the human exploration and development of space (HEDS). Note that while the task of the committee was limited to considering these particular areas, this should not be construed as a statement that there are no other new areas that might be of relevance to NASA’s mission. In choosing topics in these areas, the committee was careful to ensure that they conform to the criteria listed in Chapter 2.2 The examples provided are few in number as it is anticipated that many others will emerge from the research community.

A unifying theme of nearly all the research in these areas is that the processes of interest occur at the nanoscale. The potential of the accelerating number of discoveries of nanoanalytical tools and nanoscale phenomena, as well as their technological significance and social and ethical implications, have been explored recently in a series of workshops and reports that are now available to the public. These include the reports of the Interagency Working Group on Nanoscience, Engineering and Technology (Siegel et al., 1999; Roco et al., 2000); the report of the National Science Foundation workshop “Societal and Ethical Implications of Nanoscale Science and Nanotechnology” (Roco and Bainbridge, 2001); and the report of the National Institutes of Health workshop “Nanoscience and Nanotechnology: Shaping Biomedical Research” (NIH, 2000). According to the report issued by the National Science and Technology Council of the Executive Office of the President of the United States (NSTC, 2000), “Nanoscale science and engineering promises to become a strategic, dominant technology in the next 10– 20 years, because control of matter at the nanoscale underpins innovation and progress in most industries, in the economy, in health and environmental management, in quality of life, and in national security.” Hundreds of experts in academia and industry have made significant contributions to the above-mentioned reports, the content of which is highly relevant to the Physical Science Division, and U.S. funding agencies are well prepared to make major investments to foster these emerging technologies.

Because NASA is expected to have limited resources to invest in nanoscale materials and processes, biomolecular physics and chemistry, cellular biophysics and chemistry, and integrated systems for HEDS, it must invest in research that will enable it to utilize its resources for maximum impact. Thus, the Physical Science Division has to find unique technical niches in support of NASA’s core missions to achieve low-cost space exploration, establish permanent human presence in space, and benefit human life on Earth. For example, novel insights into nanoscale phenomena and the availability of an increasing number of nanoanalytical tools will have a major impact on NASA’s ability to generate and store power in space, manufacture lightweight materials on the ground and in space, design materials with integrated sensory functions, and develop new sensor technologies. The confluence of the biological, physical, and engineering sciences at the nanoscale is an ideal area in which NASA can effectively leverage the investments made by NSF, NIH, and other organizations to accelerate its own mission. Further, the committee believes that these areas do provide promising opportunities for researchers to build on PSD scientific capabilities and for PSD to leverage its current research activities.

1

More specific topics will be considered in Phase II.

2

It should be noted, however, that a comparision of similar research in other government programs would have to be based on specific topics, rather than the general topics discussed here.

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3
New Opportunities at the Nanoscale and at the Interface Between Biology and the Physical and Engineering Sciences
In addition to developing a broad mission statement and guidelines for selecting topics in new research areas (see Chapter 2), the Committee on Microgravity Research was also asked in this Phase I task to identify in general terms the research opportunities in the newly added discipline areas that could appropriately be pursued by the program.1 These new areas encompass still-emerging fields and thus can be characterized in various ways. In this report, they are referred to as nanoscale materials and processes, biomolecular physics and chemistry, cellular biophysics and chemistry, and integrated systems for the human exploration and development of space (HEDS). Note that while the task of the committee was limited to considering these particular areas, this should not be construed as a statement that there are no other new areas that might be of relevance to NASA’s mission. In choosing topics in these areas, the committee was careful to ensure that they conform to the criteria listed in Chapter 2.2 The examples provided are few in number as it is anticipated that many others will emerge from the research community.
A unifying theme of nearly all the research in these areas is that the processes of interest occur at the nanoscale. The potential of the accelerating number of discoveries of nanoanalytical tools and nanoscale phenomena, as well as their technological significance and social and ethical implications, have been explored recently in a series of workshops and reports that are now available to the public. These include the reports of the Interagency Working Group on Nanoscience, Engineering and Technology (Siegel et al., 1999; Roco et al., 2000); the report of the National Science Foundation workshop “Societal and Ethical Implications of Nanoscale Science and Nanotechnology” (Roco and Bainbridge, 2001); and the report of the National Institutes of Health workshop “Nanoscience and Nanotechnology: Shaping Biomedical Research” (NIH, 2000). According to the report issued by the National Science and Technology Council of the Executive Office of the President of the United States (NSTC, 2000), “Nanoscale science and engineering promises to become a strategic, dominant technology in the next 10– 20 years, because control of matter at the nanoscale underpins innovation and progress in most industries, in the economy, in health and environmental management, in quality of life, and in national security.” Hundreds of experts in academia and industry have made significant contributions to the above-mentioned reports, the content of which is highly relevant to the Physical Science Division, and U.S. funding agencies are well prepared to make major investments to foster these emerging technologies.
Because NASA is expected to have limited resources to invest in nanoscale materials and processes, biomolecular physics and chemistry, cellular biophysics and chemistry, and integrated systems for HEDS, it must invest in research that will enable it to utilize its resources for maximum impact. Thus, the Physical Science Division has to find unique technical niches in support of NASA’s core missions to achieve low-cost space exploration, establish permanent human presence in space, and benefit human life on Earth. For example, novel insights into nanoscale phenomena and the availability of an increasing number of nanoanalytical tools will have a major impact on NASA’s ability to generate and store power in space, manufacture lightweight materials on the ground and in space, design materials with integrated sensory functions, and develop new sensor technologies. The confluence of the biological, physical, and engineering sciences at the nanoscale is an ideal area in which NASA can effectively leverage the investments made by NSF, NIH, and other organizations to accelerate its own mission. Further, the committee believes that these areas do provide promising opportunities for researchers to build on PSD scientific capabilities and for PSD to leverage its current research activities.
1
More specific topics will be considered in Phase II.
2
It should be noted, however, that a comparision of similar research in other government programs would have to be based on specific topics, rather than the general topics discussed here.

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The Mission of Microgravity and Physical Sciences Research at NASA
Listed below are some broad areas of opportunity within the PSD’s newly added research fields. More specifics research topics will be explored by the committee in the Phase II report.
NANOSCALE MATERIALS AND PROCESSES
Recent technological advances have made it possible to engineer materials on length scales between 1 and 100 nm. This permits new materials to be produced that are endowed with properties and functionalities not possible with bulk large-grained materials. Nanoscale materials and processes can be expected to alter fundamentally the manner in which space is explored and will have an impact on all of NASA’s activities. Since this is a vast and rapidly changing field, the PSD should be selective in choosing research topics that will have the maximum impact on NASA’s missions and are consistent with the criteria given above. A few examples that satisfy these criteria are listed below:
Nanoparticle Formation. New materials with novel properties are essential to achieving NASA’s goal of low-cost spaceflight and establishing a permanent human presence in space. One promising area of research is the production of new materials via the consolidation of nanoparticles. Here one reaps the benefits of novel materials properties derived from the constituent nanosized particles while still allowing applications that require bulk material. These materials can exhibit unique structural, magnetic, or gas-barrier properties. A major impediment in the application of nanostructured materials is the difficulty of synthesizing nanoparticles. A method for producing materials requires that the surfaces of the particles be functionalized with molecules to yield the desired self-assembly—for example, the orientation of and interaction between the particles. Thus, it is necessary to investigate the methods used to functionalize particles. This work draws on the PSD research portfolio in the areas of crystal growth and surface and interface chemistry.
Integrated Nanomaterials. Integrating nanoscale objects is frequently necessary to obtain devices or materials with the novel properties that NASA’s mission requires. Examples of such materials range from those with integrated sensory functions to high-strength, low-weight materials. The challenges in producing such materials abound. For example, high-strength low-weight materials using composites of carbon nanotubes in a metallic matrix require dispersing individual nanotubes within a matrix. Promising routes to integrating nanoscale objects into larger devices or materials include self-assembly of the nanoscale objects on a surface or directed self-assembly using templates such as the block copolymers that are employed to control the nucleation and growth of an inorganic biomaterial. It is also possible to use DNA as a structural material to connect and control the self-assembly of particles or even nanotubes. Such work could utilize the PSD program’s expertise in surface and interface chemistry.
Micro- and Nanofluidics. Development of microanalytical devices—the so-called “chemlab on a chip”—will be a much needed technology for a vast array of both human and robotic spaceflight applications. Control of fluid flow and transport of components in the fluid phase will play important roles in the operation of such microreactors and miniaturized analysis systems. In addition, three-dimensional liquid microstructures can be produced by using patterned substrates and the spatial distribution and geometry of channels in the chip. Such microstructures alter dramatically the properties of the microfluidic device. The study of the flow processes and microstructure formation in these devices follows as a natural extension of existing work in the PSD fluid physics program.
BIOMOLECULAR PHYSICS AND CHEMISTRY
Research in biomolecular physics and chemistry can be viewed as the development of an interdisciplinary research program that will bring together physics, chemistry, biology, and materials

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science. This area has much to offer when it comes to making significant contributions to NASA goals. The important impacts will come from novel insights into molecular assembly processes, combined with nanofabrication tools, the exploitation of design principles inspired by nature, and the integration of biological and synthetic building blocks to create unique systems. The examples discussed below illustrate the potential translation of biological concepts into engineering designs that meet NASA’s goals.
Proteins in Confined Space. Long-term preservation of protein function is essential to utilize proteins in devices such as sensors, diagnostics, and bioreactors on extended flight missions. First indications exist that the native protein structure may be stabilized if it is immobilized in nanoengineered environments. Exploring the underlying mechanisms by which the structure of proteins is stabilized by confinement requires interdisciplinary teams to engineer nanostructured environments and immobilize proteins, as well as analytical techniques and theory to assess the impact of local confinement on protein conformation and function. Some of the expertise to address this challenge already exists within NASA’s protein crystallization community concerned with protein structure and protein-protein interactions. This topic could also be expanded to include the stabilization of RNA structures that have been shown to exhibit catalytic activity.
Energy Storage and Chemically Driven Nanosystems. Integration of nanoscale systems requires efficient means to generate power and to transport energy at the nanoscale. Inspired by nature, which uses energy stored in the covalent phosphate bonds of adenosine triphosphate (ATP)3 to power its nanoscale devices, NASA may explore innovative technologies for systems integration at the nanoscale (i.e., by exploring new avenues to power nanosystems chemically, rather than by conventional hard wiring). This requires expertise in areas such as fluid flow at small scales and molecular self-assembly that are already funded through programs in the PSD. This approach could yield energy storage devices with the ability to store orders-of-magnitude higher energies. The expertise can also be used to power microfabricated systems, such as robotic insects, as well as for systems manufactured or self-assembled at the nanoscale.
Smart and Self-Healing Materials. “Smart,” as well as self-healing, materials are inherent to living systems and, if available for industrial application, could revolutionize NASA’s materials of choice. New avenues have to be explored, potentially by borrowing design principles from nature, to developing responsive and self-repairing materials and systems for space applications. This could include the use of complex fluids with pressure-driven self-healing properties or the integration of active transport systems into structural materials and devices to shuttle nanocargo, potentially against concentration gradients, and/or to develop other methods to assemble and reconfigure materials properties on demand in a noninvasive manner. Furthermore, it may be possible to integrate molecules and nanoscale particles as reporters into structural materials to monitor materials properties in real time. This would make lighter and safer materials for space exploration and would have a major impact on the quality of life on Earth and in space. This program could capitalize on the strong materials science expertise of the PSD.
CELLULAR BIOPHYSICS AND CHEMISTRY
One of the toughest challenges faced by NASA is maintaining human health and handling medical emergencies in space. NASA is the only agency with a vested interest in learning how human health is affected by low-gravity conditions. An example is the need to develop countermeasures to address the rapid loss in bone mass and the muscle atrophy that are encountered during long-duration spaceflight. Although many of the low-gravity-related medical phenomena are well documented, little insight exists into the underlying cellular and potentially molecular mechanisms. Further research into the
3
Up to 7 kcal per bond.

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role of gravity in molecular recognition and cell signaling is required, and significant new insights are expected based on the rapid advances of novel nanoanalytical and biotechnology tools. Since the volume of U.S. research in this area is already enormous and is significant even within other divisions of NASA, the PSD can have the most impact by focusing on the pertinent physical aspects of these processes. Specifically, the following research areas can be explored.
Long-term Stabilization of Cell Cultures. Cells cultured ex vivo often lose their phenotype after short time periods. This limits their usefulness in bioreactors and their integration into sensors and other devices. Considerable new insights are needed to engineer proper cell environments with respect to biochemistry and to the topography of the supporting surface. These environments may be engineered at the micro- or nanoscale. Furthermore, the problem of cell starvation must be addressed through consideration of the micro- and nanoscale fluidics that will ensure that the conditions required for growth are maintained. The PSD can capitalize on its existing expertise in biotechnology, surface chemstry, materials science, and fluid physics to address this issue.
Low-Gravity Effects on Cellular and Subcellular Processes. The reasons that significant and continuous bone loss is intimately linked to prolonged exposure of astronauts to a microgravity environment are not well understood. Bone loss is only one of many other poorly understood physiological and cellular processes that are affected by the loss of gravity. At the cellular and particularly the molecular levels, little is known about how mechanical forces affect cell signaling and gene expression. New insights from molecular biology, combined with the availability of novel nanoanalytical tools, promise to rapidly advance our knowledge base about the underlying causes by which the loss of gravity ultimately affects human health. NASA has already contributed to this field—for instance, in the development of rotating bioreactors and through the study of three-dimensional cell cultures in space. Further research is required to understand how low gravity affects cell-cell interaction and communication, the interaction of a cell with an engineered environment (e.g., a solid support), and the transport of nutrients to the cell. Since the mechanical forces are typically induced or transmitted by the supporting matrix or fluid shear, a collaborative program linking fluid dynamicists and biologists is required to make the most rapid progress in this area. Major efforts are under way at NIH to understand how cells function as systems—the field of proteomics—and NASA’s contribution should be to investigate the impact of low-gravity conditions on cells as systems and to learn how to employ this knowledge to potentially contribute to the field of tissue engineering.
INTEGRATED SYSTEMS FOR HEDS
Nanotechnology at the interface with and inspired by biology has much to offer when it comes to addressing the challenges of human space exploration over extended time periods, including advanced life support systems, human health monitoring, human waste management, management of accidents and hazardous conditions, water purification, and food production, to name a few. One must capitalize on emerging technologies such as those discussed in previous sections such that they can be integrated to produce innovative systems with application to advanced space technology. This requires that multidisciplinary expertise is built into these emerging areas and that engineers are involved early on, to ensure successful integration into operational systems. One example of this includes nanoengineered and biomimetic sensor materials with advanced properties and functions that allow for in situ monitoring of humans in space. The development and application of sensors could be extended for the rapid treatment of diseases and injuries—a facility that will be needed for long-term human space travel. Forming an alliance with NIH would be an attractive way for NASA to further explore this frontier.